title: Radiation up-regulates the expression of VEGF in a canine oral melanoma cell line.
abstract: To evaluate radiosensitivity and the effects of radiation on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors in the canine oral melanoma cell line, TLM 1, cells were irradiated with doses of 0, 2, 4, 6, 8 and 10 Gray (Gy). Survival rates were then determined by a MTT assay, while vascular endothelial growth factor receptor (VEGFR)-1 and -2 expression was measured by flow cytometry and apoptotic cell death rates were investigated using an Annexin assay. Additionally, a commercially available canine VEGF ELISA kit was used to measure VEGF. Radiosensitivity was detected in TLM 1 cells, and mitotic and apoptotic cell death was found to occur in a radiation dose dependent manner. VEGF was secreted constitutively and significant up-regulation was observed in the 8 and 10 Gy irradiated cells. In addition, a minor portion of TLM 1 cells expressed vascular endothelial growth factor receptor (VEGFR)-1 intracellularly. VEGFR-2 was detected in the cytoplasm and was down-regulated following radiation with increasing dosages. In TLM 1 cells, apoptosis plays an important role in radiation induced cell death. It has also been suggested that the significantly higher VEGF production in the 8 and 10 Gy group could lead to tumour resistance.
authors.affiliation: Clinic for Internal Medicine and Infectious Diseases, Institute of Immunology, University of Veterinary Medicine, 1210 Vienna, Austria. Irene.flickinger@vetmeduni.ac.at
authors.forename: Irene
authors.initials: I
authors.lastname: Flickinger
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Rütgen
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Gerner
authors.forename: Ivana
authors.initials: I
authors.lastname: Calice
authors.forename: Alexander
authors.initials: A
authors.lastname: Tichy
authors.forename: Armin
authors.initials: A
authors.lastname: Saalmüller
authors.forename: Miriam
authors.initials: M
authors.lastname: Kleiter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor / Q000528:radiation effects; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C022616:thiazolyl blue
keywords: TLM 1; cell line; radiation; vascular endothelial growth factor